Triethylamine → HCID 69206519, compound

HRID 2252848Notes

Reaction equation

HRID 2252848 reaction equation
Cl[C:2]1[N:21]=[CH:20][CH:19]=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][CH:8]=[CH:9][C:10]1[CH:11]=[N:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=1)=[O:5].C(N(CC)CC)C>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH3:17][O:16][C:13]1[N:12]=[CH:11][C:10]([CH2:9][C:8]2[C:2]3[N:21]=[CH:20][CH:19]=[CH:18][C:3]=3[C:4](=[O:5])[NH:6][CH:7]=2)=[CH:15][CH:14]=1.[CH3:17][O:16][C:13]1[N:12]=[CH:11][C:10]([CH:9]=[C:8]2[C:2]3[N:21]=[CH:20][CH:19]=[CH:18][C:3]=3[C:4](=[O:5])[NH:6][CH2:7]2)=[CH:15][CH:14]=1

Participants

8

Reactant 2

HCID 8471TriethylamineHCID 73691356HCID 73691356, compound

Product 2

HCID 20636431HCID 20636431, compoundHCID 69206519HCID 69206519, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 67553Tetrabutylammonium IodideCatalystHCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

Under a N2 atmosphere, 1.02 g (3.36 mmol) of an (E/Z) mixture of 2-chloro-N-[3-(6-methoxy-pyridin-3-yl)-allyl]-nicotinamide, 995 mg (3.36 mmol) of tetrabutylammonium chloride, 1240 mg (3.36 mmol) of tetrabutylammonium iodide and 80 mg (0.36 mmol) of palladium diacetate are dissolved in 63 ml of DMF, then 1.2 ml (8.6 mmol) of triethylamine are added and stirring effected for 28 h at 150° C. in an ampulla. After adding a further 80 mg of palladium diacetate, stirring is again effected for 24 h at 150° C. The mixture is filtered and the DMF is partially evaporated on a RE. The residue is dissolved with EtOAc and diluted Na2CO3 solution, the water phase separated and extraction effected twice more with EtOAc/EtOH 9:1. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, methylene chloride/EtOAc 1:1→EtOAc) yields 8-[(6-methoxy-pyridin-3-yl)-methyl]-6H-[1,6]naphthyridin-5-one A (contaminated with ca. 25% 8-[1-(6-methoxy-pyridin-3-yl)-methylidene]-7,8-dihydro-6H-[1,6]naphthyridin-5-one B); FAB-MS: (M+H)+=268; HPLC(gradient20-100) tRef−6.0/8.3; 1H NMR (CDCl3) i.a. δ 4.12 (s, H2C—C(8) of A), 4.71 (d, 2.3 Hz, H2C(7) of B.

Workup

  1. stirringstirring
  2. waitis again effected for 24 h at 150° C
  3. filtrationThe mixture is filtered
  4. customthe DMF is partially evaporated on a RE
  5. dissolutionThe residue is dissolved with EtOAc and diluted Na2CO3 solution
  6. customthe water phase separated
  7. extractionextraction
  8. washThe organic phases are washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-b0c9ee458e8d4d5c8d59736cd6a67012
Source dataset
uspto-grants-2008_01
Patent number
US07323474B2

Reaction notes

Loading…